Device and method for determining the weight of pharmaceutical products by means of an x-ray source

ABSTRACT

The invention relates to a device ( 10; 10   a ) for determining the weight of pharmaceutical products ( 1 ), in particular of hard gelatin capsules ( 3; 3   a ) filled with a pharmaceutical ( 2 ), by means of an X-ray source (28), wherein the X-ray source ( 28 ) generates a radiation cone ( 27; 36, 37 ) which passes through at least one pharmaceutical product ( 1 ), and wherein a sensor element ( 30; 30   a ) detects the radiation of the irradiated pharmaceutical product ( 1 ) and supplies an evaluation device ( 32 ). According to the invention, a reference object ( 35; 35   a;    35   b ) is arranged in the beam path of the radiation cone ( 27; 36, 37 ), wherein the radiation of the X-rayed reference object ( 35; 35   a;    35   b ) is detected by means of the sensor element ( 30; 30   a;    30   b ) and is supplied to the evaluation device ( 32 ), and wherein the pharmaceutical product ( 1 ) and the reference object ( 35; 35   a;    35   b ) are positioned in relation to the radiation cone ( 27; 36, 37 ) in an arrangement in which they do not overlap each other in the radiation cone ( 27; 36, 37 ).

BACKGROUND OF THE INVENTION

The invention relates to a device for determining the weight of pharmaceutical products by means of an X-ray source. The invention furthermore relates to a method for determining the weight by means of a device in accordance with the invention.

A device is known from the German patent specification DE 10 2009 045 809 Al of the applicant. The known device comprises an X-ray source, which serves to determine the weight of products filled with a pharmaceutical, in particular in the form of hard gelatin capsules. In this case, the pharmaceutical product is X-rayed by the X-ray source and the radiation which penetrates the pharmaceutical object is detected by means of an image recording sensor element. An evaluation device of the aforementioned device then determines a filling weight for the pharmaceutical product from, e.g., the detected grey scale values of the image of said pharmaceutical product. The disadvantage with this process is that due to changing conditions, the values detected by the sensor element vary from image to image for one and the same pharmaceutical product. A concrete association of the image or respectively gray scale values with a certain filling weight in the capsule is thus made more difficult. In the case of consecutively recorded images, changes of this kind can only be recognized at locations whereat an unimpeded radiography is possible. The changes cannot however thereby be unambiguously compensated, particularly when detecting the filling weight by means of grey scale values.

SUMMARY OF THE INVENTION

Based on the previously described prior art, the aim underlying the invention is to further develop a device for determining the weight of pharmaceutical products by means of an X-ray source such that disturbances due to fluctuations in the overall system as well as external disturbances can be detected and compensated for, and therefore a particularly high degree of accuracy with regard to determining the weight of the pharmaceutical products is achieved. According to the invention, the aim is met by a device for determining the weight of pharmaceutical products by means of an X-ray source, said device having the features of claim 1, in that a reference object is arranged in the beam path of the radiation cone, wherein the radiation of the irradiated reference object is detected and supplied to the evaluation device, and wherein the pharmaceutical product and the reference object are positioned in relation to the radiation cone in an arrangement in which they do not overlap each other in the radiation cone. That is to say when imaging or respectively X-raying the pharmaceutical product, a reference object is also always simultaneously X-rayed; and therefore in combination with reference object, the items of image information can be reliably associated with the gray scale values of the pharmaceutical product even when fluctuations in the overall system or those caused by external disturbances occur. A particularly exact determination of the weight of the pharmaceutical product can thereby be performed.

Advantageous modifications to the inventive device for determining the weight of pharmaceutical products by means of an X-ray source are specified in the dependent claims. All combinations from at least two features disclosed in the claims, the description and/or the figures fall within the scope of the invention.

Provision is made in a preferred embodiment of the invention for the sensor element to be designed as an image recording sensor element. Using such an image recording sensor element, the pharmaceutical product to be examined can be very easily divided up into image points (pixels), from which items of information for the evaluation device can be obtained via the gray scale values in order to determine the weight of the pharmaceutical product.

An embodiment of the reference object, in which the material of said reference object has a similar atomic composition as the pharmaceutical product, is particularly preferred. The same physical properties as for the pharmaceutical product thus result when X-raying the reference object, and therefore the obtained items of image information about the reference object can be used directly for determining the weight of the pharmaceutical product without complicated conversions or correction factors.

An embodiment of the invention is furthermore preferred, in which the reference object is arranged in the same plane as the pharmaceutical product. In so doing, preconditions for the radiography which are at least approximately the same are created for the reference object and the pharmaceutical product with respect to the radiation cone or the X-ray radiation.

In order to be able to produce different gray scale values on the recorded image by means of the reference object, provision is made in a preferred manner for the reference object to have different thicknesses in a plane perpendicular to the beam path of the X-ray source. Different gray scales are produced by means of said different thicknesses in the image of the X-rayed reference object, which is detected by the sensor element.

Such gray scales can be constructively produced in a particularly simple and reproducible manner by means of the reference object if said reference object is designed in steps or wedge-shaped. In this way, discrete gray scales can be achieved on the image of the X-rayed reference object by means of a stepped configuration, wherein the number of steps or respectively stairs should be selected as large as possible in order to improve the resolution or to increase the measuring accuracy. As an alternative, a wedge-shaped reference object can also be used, which continually produces varying gray scale values by means of the wedge-shaped form thereof

In order to be able to evaluate all detected gray scale values or respectively gray scale levels of the X-rayed pharmaceutical product, provision is furthermore made in a particularly preferred manner for the reference object to produce a damping of the X-rays, which is larger at one location and smaller at another location than the damping produced by the pharmaceutical product. In so doing, it is ensured that all gray scale values normally occurring when X-raying the pharmaceutical product are covered by means of the reference object.

In order to maximize the individual steps of the reference object or respectively the surface thereof in a stepped or wedge-shaped configuration, provision is furthermore made in a particularly preferred manner for the surface of the reference object to be perpendicularly aligned to the radiation cone.

The invention also comprises a method for determining the weight of pharmaceutical products by means of a device according to the invention. Provision is thereby made for the pharmaceutical product and the reference object to be simultaneously X-rayed by means of an X-ray source, for an image of the X-rayed pharmaceutical product and the reference object to be supplied to the evaluation device by means of at least one image recording sensor element, for the evaluation device to examine the X-rayed pharmaceutical product pixel by pixel for the gray scale value thereof, for the same gray scale value on the reference object and thereby a thickness of the reference object to be associated with the respective pixel, for a virtual volume of the pharmaceutical product to be calculated thereafter in knowledge of the number and the surface area of the pixels and in a final step with the aid of the average thickness for the virtual volume of the pharmaceutical product to be multiplied by the thickness of pharmaceutical product in order to determine the weight of said pharmaceutical product.

A method is particularly preferred, in which the gray scale values of the reference object in consecutive images are compared with each other. In the case of a deviation, a correction factor is applied to the current gray scale values of the reference object. It is thereby ensured that the device readjusts itself even in the case of a lengthy operation thereof, in which parameters change as a result of a change in the overall system or external disturbances.

BRIEF DESCRIPTION OF THE DRAWINGS

Further advantages, features and details of the invention result from the following description of preferred exemplary embodiments as well as on the basis of the drawings.

In the drawings:

FIG. 1 shows a simplified longitudinal section of a device for determining the weight of hard gelatin capsules,

FIG. 2 shows a simplified top view of a device, which is modified with respect to FIG. 1, utilizing reference objects according to the invention,

FIGS. 3 and 4 show in each case simplified sections through different embodiments of a reference object according to the invention and

FIG. 5 shows an image of the device pursuant to FIG. 2, which is recorded by means of an image recording sensor.

DETAILED DESCRIPTION

The same components or components having the same function are provided with the same reference numerals in the figures.

In FIG. 1, the basic design of a device 10 for determining the weight of pharmaceutical products 1 is depicted. The pharmaceutical products 1 in this case relate particularly to hard gelatin capsules filled with a pharmaceutical and as the case may be with auxiliary substances or additives. It is however also within the scope of the invention to determine the weight, e.g., of tablets or something similar using the device.

The device 10 comprises an impeller 12 which is rotated in a vertical axis of rotation in discrete steps and is only depicted in part in FIG. 1. A plurality of receptacles, which receive respectively one pharmaceutical product, are vertically aligned and are designed as bore holes, are located on the upper side of said impeller, wherein only one receptacle can be seen in FIG. 1. A through bore-hole having a smaller diameter than the receptacle 13 is configured at the base of said receptacle 13.

During a standstill phase of said impeller 12, at least one receptacle 13 is positioned beneath a tubular conveyor shaft 15 by means of the progressively rotated impeller 12. On the side facing the receptacle 13, the conveyor shaft 15 comprises a section having a reduced diameter, the diameter of which is dimensioned such that a hard gelatin capsule situated in the region of the section 16 is in force-locking connection with said section 16, i.e. is clamped in said section 16. Beneath the through-bore hole, an insertion plunger 18 which moves up and down corresponding to the double-headed arrow 17 is arranged on the side facing away from the conveyor shaft 15. The hard gelatin capsule 3 situated in each case in the receptacle 13 is pushed out of the receptacle thereof 13 over into a region above the section 16 of the conveyor shaft 15 so that the impeller 12 can be further rotated in order to dispense the next hard gelatin capsule(s) without the hard gelatin capsule 3, which was last pushed over into the conveyor shaft 15, falling downwards out of said conveyor shaft 15 as a result of the weight force thereof.

The conveyor shaft 15 has a cross section, which is adapted to the cross section of the hard gelatin capsule 3 or rather somewhat larger than this. In the exemplary embodiment, the conveyor shaft 15 or respectively the longitudinal axis thereof is vertically arranged together with the longitudinal axes 19 of the hard gelatin capsules. A flap 22, which can be pivoted back and forth corresponding to the double-headed arrow 21, is arranged at the upper end of the conveyor shaft 15, said flap delivering the respective hard gelatin capsule 3 that has been pushed out of the conveyor shaft 15 either to a first discharge channel 23 or a second discharge channel 24, depending on the position of the flap 22. In so doing, those hard gelatin capsules, which are evaluated as “good” hard gelatin capsules 3, are conveyed further via the first discharge channel 2; whereas those hard gelatin capsules 3, which are evaluated as “bad” hard gelatin capsules 3, are conveyed further via the second discharge channel 24.

The conveyor shaft 15 comprises a section 26 which is permeable to x-radiation in a somewhat central region. The section 26 is radiographed by the radiation cone 27 of an X-ray source, the central radiation axis of which is preferably but not restrictively horizontally aligned, i.e. runs perpendicularly to the longitudinal axis 19. A detector in the form of an image recording sensor element 30, which is connected via a cable 31 to the evaluation device 32, is arranged on the side of the section 26 opposite to the X-ray source 28. The evaluation device 32 simultaneously serves to at least indirectly actuate the position of the flap 22.

The weight of the pharmaceutical 2 in the hard gelatin capsule 3 is determined by means of the X-ray source 28, the sensor element 30 and the evaluation device 32 in combination with a reference object 35, which is to be explained later in greater detail and which cannot be seen in FIG. 1 because it is situated in a plane perpendicular to the drawing plane of FIG. 1. Therefore (besides if need be other criteria), the result serves the purpose of distinguishing “good” hard gelatin capsules 3 from “bad” hard gelatin capsules 3.

The modified device 10 a depicted in FIG. 2 differs from FIG. 1 by the fact that the device 10 a has two X-ray sources arranged next to one another, the radiation cones 36, 37 of which in each case simultaneously pass through a plurality of hard gelatin capsules 3, in the exemplary embodiment respectively six hard gelatin capsules 3, as well as in each case a reference object 35. Two separate image recording sensor elements 30 a are thereby arranged on the side of the hard gelatin capsules 3 opposite to the X-ray sources 28 so that each of the sensor elements 30 a is associated with an X-ray source 28.

Of course, it is also within the scope of the invention for both X-ray sources 28 to use a common image recording sensor element 30 a.

The one reference object 35, which is associated with the radiation cone 36, is situated in the top view at the left edge region of the radiation cone 36, while the other reference object 35, which is associated with the radiation cone 37, is situated on the right edge of the radiation cone 37. It can furthermore be seen that the two reference objects 35 are located with respect to the respective radiation cone 36, 37 in the same plane as the hard gelatin capsules 3 to be radiographed. It is also important that the arrangement of the reference objects 35 in the respective radiation cone 36, 37 is configured in such a way that the reference objects 35 and the hard gelatin capsules 3 do not overlap each other.

Different embodiments of a reference object 35 a, 35 b are depicted in FIGS. 3 and 4. The reference object 35 a, 35 b advantageously consists of a material which has similar atomic properties as the pharmaceutical product 1 to be radiographed, i.e. particularly has the same damping properties for the x-radiation. It can furthermore be seen that both reference objects 35 a, 35 b have different thicknesses with regard to their cross sections. Whereas the reference object 35 a is thereby designed wedge-shaped, the reference object 35 b has a series of steps 38, which cause a discrete change in the thickness of the reference object 35 b. Provision is preferably made for the damping (gray scale value) of the reference object 35 a, 35 b to be greater at one location and smaller at another location than the damping by means of the pharmaceutical product 1. The arrangement or respectively the alignment of said reference objects 35 a, 35 b with respect to the radiation cone 36, 37 is furthermore configured in such a way that said reference objects 35 a, 35 b are arranged perpendicularly to their surface facing the X-ray source 28, i.e. perpendicularly to the steps 38 of said reference object 35 b or perpendicularly to the base 40 of said wedge- shaped reference object 35 a.

As is especially apparent in FIG. 2, the arrangement of the reference object 35 a, 35 b in the respective edge region of the radiation cone 36, 37 is therefore configured such that said reference object 35 a, 35 b has to be disposed in each case somewhat obliquely in order to facilitate the previously addressed perpendicular radiographing or respectively X-raying of the reference object 35 a, 35 b.

By means of the previously addressed geometric configuration of the reference objects 35 a, 35 b, said objects have different thicknesses, which produce different gray scale values at the sensor element 30 when radiographing with the X-ray source 28. In this connection, reference is made to FIG. 5, in which the images of the device 10 a pursuant to FIG. 2, which are recorded via two sensor elements 30 a, are depicted in a simplified manner. Both reference objects 35 b, which are configured in steps in the exemplary embodiment depicted, can be seen on the left or the right image edge. It is also apparent that the individual steps 38 have different gray scale values. A plurality of hard gelatin capsules 3 containing the pharmaceutical 2, which likewise has a certain gray scale value, can furthermore be seen in each respective section of the image

The determination of the weight of the pharmaceutical 2 situated in a hard gelatin capsule 3 is explained below as follows: An image of the reference object 35 a, 35 b is recorded in a calibration process, which has previously taken place and is not depicted, and the gray scale values thereof detected by the sensor device 30, 30 a are associated with the thicknesses of the reference object 35 a, 35 b on the basis of the known geometric configuration of said reference object 35 a, 35 b. In other words, this means that a certain thickness of said reference object 35 a, 35 b at a certain location is inferred on the basis of a certain gray scale value of said reference object 35 a, 35 b. Furthermore, based on the known geometry and the known material properties of said reference object 35 a, 35 b, a certain density can thereby be associated with a certain gray scale value of said reference object 35 a, 35 b.

These gray scale values previously determined in the calibration process as well as the geometric association thereof with the reference object 35 a, 35 b are stored in the evaluation device 32.

If, for example, the weight of the pharmaceutical 2 of the hard gelatin capsule denoted in FIG. 5 with the reference numeral 3 a is now detected or respectively checked, the image of the hard gelatin capsule detected by the sensor element 30 a is divided up into individual image points (pixels). Each pixel represents a certain surface area, for example a square having an edge length of 100 μm. Then the detected gray scale value of the pixel is associated with an (identical) gray scale value on the reference object 35 a, 35 b for every pixel of the hard gelatin capsule. A certain thickness can be associated with said gray scale value (on the basis of the association of the thicknesses with the gray scale values on the reference object 35 a, 35 b). After this process has taken place pixel by pixel, an average thickness is determined from the individual thicknesses. Said average thickness is now multiplied by the overall number of pixels and the known surface area thereof, and therefore a virtual volume of the pharmaceutical 2 can be determined. With knowledge of the density of the pharmaceutical 2, the weight of the pharmaceutical 2 situated in the hard gelatin capsule 3 a can finally be determined from the virtual volume.

It is also essential for an image of the relevant reference object 35 a, 35 b to be recorded in each case at the same time that the pharmaceutical product 1 is being x-rayed. In so doing, changes in the gray scale values on the reference object 35 a, 35 b can be determined on temporally consecutive images. Said changes can occur as a result of disturbances in the system or as a result of external interferences. Should, for example, it be determined that the gray scale value of the reference object 35 b changes at a certain step, the evaluation device 32 can then subject said detected, current gray scale value to a correction factor, which adapts the current gray scale value to the original gray scale value and consequently compensates for the interferences.

The devices 10, 10 a described to this point can be altered or modified in many ways without deviating from the thought underlying the invention. It is, however, important for the image of a reference object 35, 35 a, 35 b to in each case be simultaneously recorded when measuring the weight of the pharmaceutical product 1, said image being used to determine the weight of the pharmaceutical product 1. It is thus, for example, conceivable for the pharmaceutical products 1 not to be radiographed in a direction which runs perpendicularly to the longitudinal axis 19 thereof. The reference object 35, 35 a, 35 b can also basically be arranged in any position in the beam path of the X-ray source 28. 

1. A device (10; 10 a) for determining the weight of pharmaceutical products (1), by means of an X-ray source (28), wherein the X-ray source (28) generates a radiation cone (27; 36, 37) which passes through at least one pharmaceutical product (1), and wherein a sensor element (30; 30 a) detects radiation of the irradiated pharmaceutical product (1) and supplies an evaluation device (32), characterized in that a reference object (35; 35 a; 35 b) is arranged in a beam path of the radiation cone (27; 36, 37), wherein radiation of the X-rayed reference object (35; 35 a; 35 b) is detected by the sensor element (30; 30 a; 30 b) and is supplied to the evaluation device (32), and wherein the pharmaceutical product (1) and the reference object (35; 35 a; 35 b) are positioned in relation to the radiation cone (27; 36, 37) in an arrangement in which the pharmaceutical product and the reference object do not overlap each other in said radiation cone (27; 36, 37).
 2. The device according to claim 1, characterized in that the sensor element is an image recording sensor element (30; 30 a; 30 b).
 3. The device according to claim 1, characterized in that a material of the reference object (35; 35 a; 35 b) has a similar atomic composition as the pharmaceutical product (1).
 4. The device according to claim 1, characterized in that the reference object (35; 35 a; 35 b) is arranged in the same plane (39) as the pharmaceutical product (1).
 5. The device according to claim 1, characterized in that the reference object (35; 35 a; 35 b) has different thicknesses in a plane perpendicular to the radiation cone (27; 36, 37).
 6. The device according to claim 5, characterized in that the reference object (35 a, 35 b) is designed wedge-shaped or in steps.
 7. The device according to claim 5, characterized in that the reference object (35; 35 a; 35 b) produces a damping of x-radiation which is greater at one location and smaller at one location than the damping produced by the pharmaceutical product (1).
 8. The device according to claim 5, characterized in that a surface of the reference object (35; 35 a; 35 b) is perpendicularly aligned to the radiation cone (27; 36, 37).
 9. A method for determining the weight of pharmaceutical products (1) by means of a device (10; 10 a) according to claim 1, characterized in that the pharmaceutical product (1) and the reference object (35; 35 a; 35 b) are simultaneously radiographed by means of the X-ray source (28), in that an image of an irradiated pharmaceutical product (1) and of the reference object (35; 35 a; 35 b) are supplied to the evaluation device (32) by at least one image recording sensor element (30; 30 a), in that the evaluation device (32) examines the irradiated pharmaceutical product (1) pixel by pixel for a gray scale value thereof and associates the same gray scale value on the reference object (35; 35 a; 35 b) and thereby a thickness of said reference object (35; 35 a; 35 b) with the gray scale value of the respective pixel, in that an average thickness is subsequently determined across all of the pixels, in that thereafter in knowledge of a number and surface area of the pixels, a virtual volume of the pharmaceutical product (1) is calculated; and in that in a final step, the virtual volume of said pharmaceutical product (1) is multiplied by the thickness of said pharmaceutical product (1) to determine the weight of said pharmaceutical product (1).
 10. The method according to claim 9, characterized in that in the case of consecutive images, the gray scale values of the reference object (35; 35 a; 35 b) are compared with each other and in the event of a deviation, a correction factor is applied to the current gray scale value. 